SPACE PROVIDED. Multiple sclerosis (MS) and other central nervous system (CNS) neuroinflammatory diseases are characterized by early axonal injury and degeneration. While little is known about the specific biological processes that underlie axonal injury, there is clear evidence that these processes carry significant importance in disease pathogenesis. Recent findings in experimental mouse models have shown evidence for axon-specific degeneration pathways distinct from those found In the cell body. Microglia, the immune cells of the CNS, exacerbate inflammation by migrating to sites of axonal injury and upregulating the production of inflammatory molecules. The cytokine-mediated signals that recruit microglia to sites of axonal injury, as opposed to neural injury, are poorly understand but could elucidate novel mechanisms of disease maintenance and progression. The central themes of the doctoral research are to (a) design and optimize microfluidic platforms to precisely control cellular interaction and inflammatory stimuli, (b) investigate concentration-dependent roles of inflammatory mediators on axonal degeneration, and (c) characterize cellular mechanisms of microglial chemotaxis in response to axon injury. The broad significance of this research is the development of innovative technologies that will enable the discovery of important axon- specific pathways involved in CNS neuroinflammatory and neurodegenerative diseases, including MS and transverse myelitis. The research and training goals outlined in this grant will define a year-by-year plan for the applicant such that he will become an independent and successful researcher in the biomedical sciences. The methods and procedures he will learn will allow him to (a) perform and critically analyze cross-disciplinary research, (b) disseminate knowledge through written publication, (c) orally communicate research findings, (d) organize research goals through grant writing, and (e) conduct proper research practices through continued ethics training. To satisfactorily complete these objectives, the pre-doctoral student will be closely mentored by an interdisciplinary team of principal investigators in Biomedical Engineering, Neuroscience, and Neurology. A detailed plan for training and mentorship is presented. PHS 416-1 (Rev. 9/08) Page 2 Number pages consecutively at the bottom throughout Form Page 2 the application. Do not use suffixes such as 2a, 2b. NAME OF APPLICANT (Last, first, middle initial) Kirschstein-NRSA Individual Fellowship Application Hosmane, Suneil, N. (To be completed by applicant - follow PHS 416-1 instructions) 18.